Does genetic variation in PNPLA3, TM6SF2 and HSD17B13 have a role in the development or prognosis of hepatocellular carcinoma in Turkish patients with Hepatitis B?

BACKGROUND AND AIMS: Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown. MATERIALS: We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis. RESULTS: The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC. CONCLUSIONS: We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis

Appraising diagnostic performance of ELF test by pathological staging and digital quantification of liver fibrosis

Introduction and objectives: A crucial issue when appraising the performance of non-invasive markers is the limitations of the reference standard they are compared to. Digital image analysis (DIA) was suggested as a reproducible approach expressing fibrosis numerically as a proportionate area (PA) (%). We aimed to evaluate ELF test with direct reference to PA (%), thereby explore the improvement in accuracy to discriminate significant fibrosis which may actually have been underestimated by categorical pathological staging. Materials and methods: PA (%) data were obtained by DIA of trichrome-stained liver biopsies of 52 chronic hepatitis patients. Paired serum samples of patients and additional 36 controls were performed to measure ELF test. Diagnostic performance characteristics of ELF test was derived in predicting significant fibrosis in the patient cohort, and also, in distinguishing healthy controls from patients with significant fibrosis. Results: We found an AUROC value of 0.73 for ELF to predict significant fibrosis as assessed by DIA and a lower AUROC value of 0.66 when assessed by conventional pathology. Importantly, ELF test provided considerably high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis defined by Ishak F >= 2 and TPA >= 5% (AUROCs 0.93 and 0.94, respectively) with optimal ELF cut-off point of 8.4 for both. Conclusions: Digital quantification could represent a better reference standard than conventional pathology allowing a better discriminatory capability for ELF test. ELF test provided high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis suggesting a role as a screening strategy in the community setting. (C) 2019 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U

Digital image analysis in liver fibrosis: basic requirements and clinical implementation

Accurate assessment of liver fibrosis is a critical aspect of diagnosis, prognosis prediction, surveillance strategies, therapeutic planning and monitoring, and also for validation of non-invasive surrogates of fibrosis. Traditional histopathological stagings depend on subjective visual interpretation process of architectural changes of fibrosis without providing quantification as continuous numerical data, but rather in the form of discrete staging. This makes high level reproducibility practically impossible in its application, which should be minimized in scientific research. In the light of increasing demand for an objective method, digital image analysis (DIA) technology has been increasingly implemented for liver fibrosis assessment. Potential advantages and applications of reproducible quantitative fibrosis ratio measurements with DIA include performing broader scale of statistical analysis and comparison between studies, monitoring minor but potentially important quantity changes during fibrosis regression or progression (especially in the context of therapeutic trials), and to be a better histological reference standard for validity and accuracy of surrogates of fibrosis. DIA may also have a potential role within the new perspective of redefining and sub-classifying cirrhosis. Since DIA algorithm covers multiple domains of hepatopathology and engineering, it may seem to be complicated to a researcher. This review provides an understanding of all basic steps, techniques, clinical applications of computerized image analysis for the particular purpose of liver fibrosis aiming its better implementation in hepatology research. Further work is required for standardization of all stages of pre-imaging, digital image acquisition and digital image processing steps for generation of reproducible outputs

Palliative care in cirrhotic patients: Brief summary of recent AASLD guidance

Palliative care in decompensated cirrhotic patients is a developing concept which should be used in cirrhotic patients during the advanced and terminal stages. Hepatologists and liver transplant teams mostly ignore the patients palliative care issues while intensively dealing with the liver diseases and its complications. This review is a brief summary of the recently published guidance discussing the palliative care, symptom based treatments and end of life with a collaborative and standartized approach which is recommended to all health care workers of cirrhotic patients